Related Experiment Video
Updated: Jun 28, 2026

Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents
Published on: May 16, 2022
The discovery of highly potent CGRP receptor antagonists
Craig A Stump1, Ian M Bell, Rodney A Bednar
1Department of Medicinal Chemistry, Merck & Co, Inc, West Point, PA 19486, USA. craig_stump@merck.com
Abstract:
Rational modification of a previously identified spirohydantoin lead structure has identified a series of potent spiroazaoxindole CGRP receptor antagonists. The azaoxindole was found to be a general replacement for the hydantoin that consistently improved in vitro potency. The combination of the indanylspiroazaoxindole and optimized benzimidazolinones led to highly potent antagonists (e.g., 25, CGRP K(i)=40pM). The closely related compound 27 demonstrated good oral bioavailability in dog and rhesus.
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